Key result
Amiodarone and dronedarone reduce atrial TR expression by ~50%, with amiodarone showing stronger ventricular effects.
Why the study?
Amiodarone and dronedarone have different actions on thyroid hormone receptor isoforms, and their effects on cardiac gene expression in different heart components were unclear.
Answers are grounded in this paper and cite their sources.
Rat study indicates component-specific cardiac TR effects; leaves open human translation and clinical relevance.
OBJECTIVE: In view of their different actions on thyroid hormone receptor (TR) isoforms we set out to investigate whether amiodarone (AM) and dronedarone (Dron) have different and/or component-specific effects on cardiac gene expression. DESIGN: Rats were treated with AM or Dron and the expression of TRalpha 1, TRalpha 2, TRbeta 1 and several tri-iodothyronine (T3)-regulated genes was studied in different parts of the heart, namely the right atrium (RA), left ventricular wall (LVW) and apex. METHODS: Rats were treated for 14 days with 100 mg/kg body weight AM or Dron. The expression of TRalpha 1, TRalpha 2, TRbeta 1 and T3-regulated genes was studied using real-time PCR and non-radioactive in situ hybridisation. RESULTS: AM and Dron affected TR expression in the RA similarly by decreasing TRalpha 1 and beta 1 expression by about 50%. In the LVW, AM and Dron decreased TRbeta 1 and, interestingly, AM increased TRalpha 1. In the apex, AM also increased TRalpha 2. The changes seen in T3-dependent gene expression are reminiscent of foetal reprogramming. CONCLUSION: Taken together, our results indicate that AM and Dron have similar effects on the expression of TR isoforms in the RA, which could partly contribute to their ability to decrease heart rate. On the other hand, the more profound effect of AM appears on TR- and T3-dependent gene expression in the left ventricle suggests foetal reprogramming.
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Stoykov et al. (2007) studied this question. Amiodarone and Dronedarone was evaluated on Expression of TRalpha 1, TRalpha 2, TRbeta 1 and T3-regulated genes in different parts of the heart. Amiodarone and dronedarone similarly decreased TRalpha 1 and beta 1 expression by about 50% in the right atrium, while amiodarone had more profound effects in the left ventricle.
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